|PROSITE documentation PDOC51826 [for PROSITE entry PS51826]|
The ubiquitous 2-oxoacid dehydrogenases are a family of very large multienzyme complexes consisting of multiple copies of at least three enzymes which catalyze the oxidative decarboxylation of several different 2-oxoacids, resulting in acyl-CoA products. Members of this family include pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-oxoacid dehydrogenase (BCDH). The three enzymes assembling to form these complexes are the decarboxylase E1 (called E1p, E1o and E1b in PDH, OGDH and BCDH, respectively), dihydrolipoamide acetyl, succinyl and branched-chain transferase E2 (E2p, E2o and E2b, respectively) and dihydrolipoamide dehydrogenase E3. The E3 component is identical in all three complexes (PDH, OGDH and BCDH) and catalyzes the same reaction. The structural core of all 2-oxoacid dehydrogenase complexes (ODHc) is formed of multiple copies of E2 subunits, with the E1 and E3 subunits bound on the periphery. The E2 component of the ODHc’s of both bacteria and eukaryotes serves as the structural core of these multienzyme complexes and is comprised of three types of domains. Starting with the N-terminus, there are 1–3 tandem repeated lipoyl domains (LD) (see <PDOC50968>), followed by a peripheral subunit-binding domain (PSBD) responsible for binding E1/E3 chains. The third domain is the C-terminal catalytic domain (CD). The individual domains are separated by long, flexible linker regions allowing large movements of the lipoyl domain(s) to enable active site coupling. The PSBD domain binds E1 or E3, but not both simultaneously. The flexible linker allows the PSBD domain (associated with either E1 or E3) to move quite freely with respect to the core formed E2 catalytic domains [1,2,3,4,5].
The ~35-residue PSBD domain has a compact structure consisting of two short, parallel α-helices (H1 and H2) separated by a loop (L1), a single helical turn, and a further, less well-ordered loop (L2) (see PDB:1BAL>). The compact structure of the PSBD domain is stabilized mainly by hydrophobic interactions. The interactions between the PSBD domain and E3 are all mediated by charged side chains, forming an 'electrostatic zipper'. The residues of the PSBD domain involved in the interactions are all provided by helix H1 of this domain. Helix H2 of PSBD does not interact with E3, but may be involved in binding E1 [1,2,4].
The profile we developed covers the entire PSBD domain.Last update:
January 2017 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Robien M.A. Clore G.M. Omichinski J.G. Perham R.N. Appella E. Sakaguchi K. Gronenborn A.M.|
|Title||Three-dimensional solution structure of the E3-binding domain of the dihydrolipoamide succinyltransferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.|
|2||Authors||Mande S.S. Sarfaty S. Allen M.D. Perham R.N. Hol W.G.J.|
|Title||Protein-protein interactions in the pyruvate dehydrogenase multienzyme complex: dihydrolipoamide dehydrogenase complexed with the binding domain of dihydrolipoamide acetyltransferase.|
|Title||Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions.|
|Source||Annu. Rev. Biochem. 69:961-1004(2000).|
|4||Authors||Brautigam C.A. Wynn R.M. Chuang J.L. Machius M. Tomchick D.R. Chuang D.T.|
|Title||Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.|
|5||Authors||Kumaran S. Patel M.S. Jordan F.|
|Title||Nuclear magnetic resonance approaches in the study of 2-oxo acid dehydrogenase multienzyme complexes--a literature review.|